This application seeks 2 years of funding to complete COMBINE and its ancillary cost-effectiveness and genetic predictors of treatment response studies. The COMBINE study was initiated in 1997 to answer questions about the benefits of combining behavioral and pharmacological interventions. Two medications, naltrexone and acamprosate, have shown promise in reducing relapse to heavy drinking and improving abstinence in a number of U.S. and European clinical trials. The two behavioral treatments, Medical Management (MM) and Combined Behavioral Intervention (CBI), have potential to be valuable adjuncts to pharmacotherapy. MM appears to be cost-effective and suitable for delivery in primary care or managed care settings by non-specialists. The primary hypothesis is that combining naltrexone and acamprosate with a moderate intensity behavioral treatment (CBI) will yield better outcomes than less intensive approaches (e.g., placebo and MM; acamprosate or naltrexone and MM). A total of 1375 subjects from 11 clinical sites comprise the targeted sample. Individuals meeting study criteria have been randomly assigned to one of 9 pharmacological and behavioral treatment combinations to form a complete 2X2X2 factorial design. A ninth cell was later included to test the efficacy of CBI without "pills." Much has been accomplished thus far. Over 70% of the intended sample has been randomized, reflecting gender, ethnic, geographic, and clinical diversity. Drinking assessment interviews have been completed for 84% of clients at 16-week follow-up. Two major pilot studies were successfully completed and the findings have been disseminated at conferences and in publications. The requested 2-year extension will allow for the recruitment, treatment, and follow-up of the remaining participants, and allow sufficient time for data analysis and manuscript preparation. Results from COMBINE are expected to have a Major Impact on the alcohol treatment system. A common protocol across each study site is submitted, reflecting the cooperative process that has guided the study. However, each study site has provided site-specific information on the budget, budget justifications, listing of key personnel, Consultant/consortium agreements, and human subjects sections of their respective proposals.